This grant aims to study the functional significance of sex differences in vasopressin innervation of the brain. The central hypothesis driving this grant is that sex differences in neurotransmitter systems may induce sex differences in overt brain functions and behaviors as well as prevent them. The latter would occur to compensate for hormonal and physiological sex differences that otherwise might cause undesirable sex differences. Parental behavior in rodents such as prairie voles (Microtus ochrogaster), in which males as well as females care for the young, is a good example. Hormonal changes associated with pregnancy prime the brain of female rodents for parental behavior. By necessity males must use a different mechanisms to prime their brain for parental behavior. This grant explores to what extent the sexually dimorphic vasopressin projections of the bed nucleus of the stria terminalis and medial amygdaloid nucleus help male and female voles to generate qualitatively similar parental behavior. These vasopressin projections are much denser in males than in females and stimulate parental behavior in males. The first aim will be to study how vasopressin or its antagonists influence parental behavior at different stages of the reproductive cycle. The prediction is that interference with vasopressin transmission should cause sex differences in behaviors that otherwise are similar. A second aim will study whether sex differences in these responses are caused by sex differences in gonadal hormone levels during development. A third aim will study whether social conditions that minimize sex differences in parental behavior also change the involvement of vasopressin in parental behavior. Finally, a fourth aim will delineate areas in the brain where vasopressin is likely to control parental behavior in a sexually dimorphic manner. It will do so by studying whether social conditions that influence parental responsiveness change vasopressin receptor occupancy as well as by studying the effects of manipulating levels of vasopressin receptor expression in different areas of the brain. By virtue of its theme, this project will increase the little knowledge currently available on the neural control of paternal behavior as well as clarify the role of sex differences in the brain. In addition, by showing that the effects of neuropeptides on behaviors are state- and sex-dependent, this study may affect drug therapies that are based on manipulating neurotransmission, because it underscores the notion that these therapies should be developed independently for men and women.